A Dutch study suggests women who test negative for the human papilloma virus (HPV), the leading cause of cervical cancer, can be safely screened once every 10 years.

Countries including the UK are currently in the process of implementing HPV testing as part of cervical screening.

The study found the long-term incidence of cervical cancer and abnormal cells was low in women who screened negative for HPV.

Researchers followed more than 40,000 women for around 14 years to assess whether HPV-based cervical screening programmes are successful enough to extend cervical screening intervals.

The research team believe their findings mean the interval between cervical screening tests can be increased to more than five years for women over 40 who have screened negative for HPV.

At the moment, cervical screening is offered to women aged 25 to 64 in England. This is every three years for women aged 25 to 49 and every five years for women aged 50 to 64.

Testing for HPV is already part of the NHS Cervical Screening Programme. The National Screening Committee is currently considering how often a woman should be offered a test for HPV.

Cervical screening can identify abnormal cells so they can be treated before cancer develops. As we discussed last month, hundreds of deaths would be prevented each year if all women in the UK attended their screening appointments.

Where did the story come from?

The study was carried out by researchers from VU University Medical Centre in Amsterdam and Erasmus MC in Rotterdam.

It was funded by the Netherlands Organisation for Health Research and Development and the European Commission.

The study was published in the peer-reviewed British Medical Journal (BMJ).

The media presented the main findings of the study accurately.

Many sources carried a quote from Dr Anne Mackie from Public Health England, who said: “The UK National Screening Committee is currently carrying out a review to identify how often a woman should be tested for HPV. A consultation on the review findings will begin next year.”

You could criticise the Daily Mail’s attitude towards these crucial tests in its introductory line: “Women could soon be spared the ordeal of having to go so often for smear tests”. While a smear test can be a bit uncomfortable for some women, it is also vitally important.

What kind of research was this?

This research presented long-term follow-up results of the POBASCAM trial, a population-based randomised controlled trial (RCT) of HPV testing for cervical screening.

This trial aimed to assess the risk of extending screening intervals to more than five years for a combined HPV and cytology-based cervical screening programme.

This is the best way of assessing risk like this, as the population was randomly assigned to groups and the findings seen are therefore less likely to be down to chance.

What did the research involve?

Women from the Netherlands aged 29 to 61 years old were invited to participate in the cervical screening programme between January 1999 and September 2002.

Half of the participants were randomly assigned to an intervention group, who had an HPV test as well as the usual cytology screen from a cervical smear.

The other half made up the control group, who were assigned to cytology and an HPV test, but the HPV test result was only made available to the researchers, not the woman or her doctor.

In the intervention group:

Women with negative HPV and cytology results were referred for routine screening every five years.

HPV-positive women with negative or borderline cytology were advised to have repeat tests after 6 and 18 months: if the cytology results were still HPV positive or moderate or worse, the women were referred for colposcopy, a procedure that allows doctors to examine the cervix more closely.

Women with moderate or worse cytology were referred for colposcopy.

In the control group:

Women with negative cytology were referred for routine screening every five years.

Women with borderline or mildly abnormal cytology were advised to repeat tests after 6 and 18 months. If they were still borderline or worse, they were referred for colposcopy.

Women with moderate or worse cytology were referred for colposcopy.

At the second round of screening after five years, both groups of women had HPV and cytology tests. Their management was based on both results, as per the initial intervention group protocol.

At the third round of screening at 10 years, all women just had management based on the cytology result.

The women were followed up for 14 years.

What were the basic results?

A total of 43,339 women were included in the study, and had an average age of 42.8 years.

The HPV test reduced the incidence of cancer.

The researchers found the incidence of cervical cancer in HPV-negative women from the intervention group after three rounds of screening was similar to the incidence in women with normal cytology in the control group after two rounds of screening at 0.09%.

After three rounds of screening, the incidence for these women from the control group had risen to 0.19%.

For women with normal cytology and a positive HPV test, the risk of cancer was 71% lower in the intervention group, though the wide confidence interval reduces reliability in this result (rate ratio 0.29, 95% confidence interval 0.10 to 0.87).

The incidence of CIN3+, where abnormal cells affect the full thickness of the lining covering the cervix, was also lower in the intervention group.

For HPV-negative women in the intervention group, the incidence was 0.56% after the third round of screening, compared with 1.2% for women with normal cytology from the control group.

The team believe HPV-based screening provides significantly better protection than abnormal cells cytology-based screening. They also feel that, compared with primary HPV testing, the value of primary HPV and cytology co-testing is limited.

They concluded that, “Long-term incidences of cervical cancer and CIN3+ were low among HPV-negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older.”

Conclusion

This long-term follow-up of women involved in the POBASCAM randomised controlled trial aimed to assess the risk of extending screening intervals to more than five years for HPV-based cervical screening programmes.

The study found that in women who were HPV negative, the long-term incidence of cervical cancer and abnormal cells was low.

The research team believes these findings mean the interval between cervical screening tests can be increased to more than five years for women over the age of 40.

This study was well designed, and included a large number of women with similar dropout rates between study arms.

But the study has a number of limitations, which the research team is aware of:

Incidence estimates of cervical cancer and abnormal cells were determined through nationwide histopathology databases. How many cases were missed because women declined the recommendation to have a colposcopy could not be assessed.

There is some risk of misclassification during diagnoses by local pathologists.

To compare risk after a negative HPV test in the intervention group at the third screening round against the risk after a negative cytology test in the control group at the second round, all cancers were detected up to 14 and 9 years after enrolment, respectively. These follow-up times are greater than the targeted screening times at 10 and 5 years.

At the moment, cervical screening is offered to women aged 25 to 64 in England. Women are invited to attend by letter from their GP. This is every three years for women aged 25 to 49 and every five years for women aged 50 to 64.

Testing for HPV has already been incorporated into the NHS Cervical Screening Programme. A further UK-based pilot study would be required if the length of time between screening for certain low-risk women was to be extended in the UK.